An HIV Prevention Program for Mochudi, Botswana Summary According to UNAIDS, Botswana has the second-highest prevalence of HIV in the world. Within Africa, Botswana has achieved the highest rates of voluntary HIV testing and of provision of free HAART and perinatal HIV transmission prevention interventions. Nevertheless, HIV prevalence/incidence have not changed significantly despite ongoing prevention and treatment efforts, and considerable local interest exists in implementation of more effective prevention interventions. We propose a comprehensive package of behavioral and biomedical interventions to 15-49-year-olds in Mochudi, a village in the south of Botswana, including (1) routine, opt-out HIV testing;(2) education to encourage behavior modification, including condom use;(3) male circumcision;and (4) three-drug HAART for HIV-infected persons with acute infections and/or high viral loads (VL). We will determine HIV prevalence and incidence using repeated screening of the entire population in Mochudi before and after implementation of interventions. Uptake of HIV testing, condom use, and other behavioral recommendations will be assessed from repeated surveys of the entire village. Uptake of the other interventions, and the sources of incident infections investigated using PCR and contact tracing, would be evaluated in the northeast section of Mochudi (population, 14,000). Viral genotyping will be performed to identify potential viral networks or clusters by sequence analysis of infected individuals. Mathematical models will be developed and parameterized to reflect the epidemic in Mochudi and updated by information from surveillance activities. These models will be used to identify potential synergies among preventive measures and to estimate what combined levels of coverage/uptake and effectiveness must be achieved to hold the effective reproductive number of the virus in the community below one. The Specific Aims are (1) to characterize the HIV epidemic in Mochudi by estimating incidence and prevalence of HIV and of behavioral risk factors at 3 time points over a 21/2-year period;(2) to determine uptakes of voluntary counseling and testing, condom use, acceptability of partner notification with contact tracing, and male circumcision;(3) to identify transmission associations with genome signature tracing to evaluate associations between transmissions and high VL;(4) to estimate the rate of acceptance of HAART offered upon detection to HIV-infected individuals with acute infection and/or VL e 100,000 who do not otherwise qualify for treatment based on national guidelines (AIDS-defining illness or CD4 <250), and to assess adherence to drug schedules and rates of baseline and new drug resistance;and (5) to develop model-based projections and assessments of the potential for epidemic control, and to use these models to evaluate the cost effectiveness of combinations of preventive interventions. An HIV Prevention Program for Mochudi, Botswana Relevance The goal of the application is to demonstrate the feasibility and acceptability of a comprehensive program of interventions to reduce HIV incidence in Mochudi, a village of 39,000 people in southern Botswana with an HIV prevalence of 25% in adults. This combination of interventions will include education for behavior modification, circumcision of adult males, and the use of antiretroviral drugs to decrease transmission at the community level. The ultimate goal is to evaluate prevention interventions that could be scaled up as public health policy in Botswana and southern Africa.